This invention relates to a substantially pure aminosterol antibiotic which can be isolated from the tissues of the common dogfish shark, Squalus acanthias.
Over the past several years, antibiotic agents have been isolated from a side range of animal species. These agents are believed to play a role in the innate immunity of an animal (Boman, H. G., Cell 65, 205-207 (1991)), and comprise a variety of antibiotic substances used in defense against environmental microbes. In certain physiological settings antibiotics are discharged onto epithelial surfaces (Bevins, C. L. et al , Annu. Rev Biochem. 59, 395-414 (1990); Samakovlis, C., et al., EMBO J. 10, 163-169 (1991); Nicolaides, N., Science, 19-26 (1974)), secreted into internal body fluids (Boman, H. G., et al., Annu. Rev. Microbiol. 41, 103-126 (1987)), or utilized within the vacuoles of phagocytic defensive cells (Lehrer, R. I., Cell 64, 229-230 (1991)). To date, only a limited number of low molecular weight antibiotics have been identified in animals, including peptides (Steiner, H. et al., Nature 292, 246-248 (1981); Ganz, T., et al., J. Clin. Invest. 76, 1427-1435 (1985); Zasloff, M., Proc. Natl. Acad. Sci. USA 84, 5449-5453 (1987)), bacteriostatic alkaloids (Daly, J. W. et al., Toxicon 25, 1023-1095 (1987); Preusser, H. J., et al., Toxicon 13, 285-289 (1975)), and lipids (Kabara, J. J., Lipids 12, 653-659 (1987); Bibel, D. J. et al., J. Invest. Dermato. 92, 632-638 (1989); Tiffany, J. M. et al., Lipid Res. (eds. Paoletti, R. and Kritchevsky, D.) 22, 1-62 (1987); Brissette, J. L. et al., J. Biol. Chem. 261, 6338-6345 (1986).